title: Hypoxamirs and mitochondrial metabolism.
abstract: CONCLUSIONS
  Chronic hypoxia can drive maladaptive responses in numerous organ systems, leading to a multitude of chronic mammalian diseases. Oxygen homeostasis is intimately linked with mitochondrial metabolism, and dysfunction in these systems can combine to form the backbone of hypoxic-ischemic injury in multiple tissue beds. Increased appreciation of the crucial roles of hypoxia-associated miRNA (hypoxamirs) in metabolism adds a new dimension to our understanding of the regulation of hypoxia-induced disease.
  
  
  BACKGROUND
  Myriad factors related to glycolysis (e.g., aldolase A and hexokinase II), tricarboxylic acid cycle function (e.g., glutaminase and iron-sulfur cluster assembly protein 1/2), and apoptosis (e.g., p53) have been recently implicated as targets of hypoxamirs. In addition, several hypoxamirs have been implicated in the regulation of the master transcription factor of hypoxia, hypoxia-inducible factor-1α, clarifying how the cellular program of hypoxia is sustained and resolved.
  
  
  RESULTS
  Central to the discussion of metabolic change in hypoxia is the Warburg effect, a shift toward anaerobic metabolism that persists after normal oxygen levels have been restored. Many newly discovered targets of hypoxia-driven microRNA converge on pathways known to be involved in this pathological phenomenon and the apoptosis-resistant phenotype associated with it.
  
  
  CONCLUSIONS
  The often synergistic functions of miRNA may make them ideal therapeutic targets. The use of antisense inhibitors is currently being considered in diseases in which hypoxia and metabolic dysregulation predominate. In addition, exploration of pleiotripic miRNA functions will likely continue to offer unique insights into the mechanistic relationships of their downstream target pathways and associated hypoxic phenotypes.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital , Boston, Massachusetts.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Cottrill
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Chan
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007501:Iron / Q000378:metabolism; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D045222:Electron Transport Chain Complex Proteins; D035683:MicroRNAs; D007501:Iron